Effects of the beige mutation and irradiation on natural resistance to marrow grafts.

Both short-term splenic and long-term systemic natural resistance to bone marrow growth in vivo may be caused by mechanisms related to those causing natural killer (NK) cell activity. To explore this relationship, the effects of the beige mutation and split-dose irradiation were studied. The former eliminated NK activity, as expected. The latter had little effect on NK activity but reduced spleen cell numbers. Both the beige mutation and split-dose irradiation reduced, but failed to eliminate resistance to short-term growth of WB or A/J marrow in spleens of lethally irradiated B6 mice. The combination of the beige mutation and split-dose irradiation in the same recipient has not been previously reported; it was much more effective than either alone in reducing this resistance. Simultaneous measurement of CFU-S numbers and spleen weights has not been previously used for quantitative measurements of natural resistance in vivo, however, in this study it proved especially effective. Over a range of marrow doses, increases in spleen weights showed that the beige mutation reduced resistance slightly more effectively than split dose irradiation, and that their combination was much more effective than either alone, but some resistance remained, as spleen weights increased fastest with low cell numbers in syngeneic recipients. Long-term resistance to systemic erythropoietic repopulation of lethally irradiated B6 recipients by WB marrow has not been previously studied. It was lower than short-term resistance in spleens and it was completely abrogated by the beige mutation alone, but only partially removed by split-dose irradiation. These results are similar to the effects of these treatments on NK cell activity, and suggest a relationship between NK cells and effector cells in long-term resistance. However, additional effector cell types appear to be involved in short-term resistance.